Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS4062976 A
Publication typeGrant
Application numberUS 05/641,730
Publication dateDec 13, 1977
Filing dateDec 18, 1975
Priority dateDec 18, 1975
Also published asCA1052274A1
Publication number05641730, 641730, US 4062976 A, US 4062976A, US-A-4062976, US4062976 A, US4062976A
InventorsEdwin B. Michaels
Original AssigneeMichaels Edwin B
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Antimicrobial compositions employing certain substituted alanines and certain t-amine oxides
US 4062976 A
Abstract
There is provided an antimicrobial composition of low toxicity having enhanced gram positive and gram negative activity and consists essentially of:
A. An alkylsubstituted alanine (0.1 part - 40.0 parts, by weight),
B. an alkyl-N,N-dimethylamine oxide, an alkyl-N,N-dihydroxyethylamine or an acylamido t-amine oxide (0.1 part - 40.0 parts, by weight), and
C. a protonating agent, such as hydrochloric acid, acetic acid or citric acid, in an amount sufficient to adjust the pH of the overall composition to about 5.5 or below.
The composition exhibits skin degerming, cleansing, and deodorizing properties and, particularly, its use exhibits long term inhibition of body odor.
Images(5)
Previous page
Next page
Claims(8)
I claim:
1. A broad spectrum, antimicrobial composition having low toxicity which consists essentially of:
a. 0.1 to 40 parts, by weight, of a higher alkylsubstituted alanine having the structure:
1 RNHCH2 CH2 COOH, or
2 RN(CH2 CH2 COOH)2
where R is a higher alkyl of from 10 to 18 carbon atoms,
b. 0.1 to 40 parts, by weight, of (1) a higher alkyl-N,N-dimethylamine oxide, (2) a higher alkyl-N,N-dihydroxyethylamine oxide, or (3) an acylamido t-amine oxide having the respective structure: ##STR2## where R1 is a higher alkyl of from 10 to 18 carbon atoms, or mixtures of the same, and
c. a protonating agent, sufficient to adjust the pH of said composition from 4 to 6.0.
2. The composition according to claim 1 wherein the N-alkylalanine is N-cocoalanine.
3. The composition according to claim 1 wherein the N-alkylalanine is N-stearylalanine.
4. The composition according to claim 1 wherein the N-alkylalanine derivative is N-coco-bis (2-aminopropionic acid).
5. The composition according to claim 1 wherein the higher alkylamine oxide is coco-N,N-dimethylamine oxide.
6. The composition according to claim 1 wherein the protonating agent is citric acid.
7. The composition according to claim 1 wherein the protonating agent is acetic acid.
8. The composition according to claim 1 wherein the composition is dissolved in an aqueous medium and wherein the pH of the aqueous mixture is adjusted to and maintained at from 4.7 to 5.2.
Description

The present invention relates to antimicrobial composition of enhanced efficacy and safety. More particularly, the invention relates to antimicrobial compositions having low toxicity and broad spectrum antimicrobial activity comprising certain amphoteric surfactants which per se have limited antimicrobial use. Still more particularly, the invention is concerned with antimicrobial compositions of enhanced gram positive and gram negative activity comprising in admixture:

A. an alkylsubstituted alanine (0.1 - 40.0 parts, by weight),

B. an alkyl-N,N-dimethylamine oxide, an alkyl-N,N-dihydroxyethylamine oxide, or an acylamido t-amine oxide (0.1 - 40.0 parts, by weight), and

C. a protonating agent, such as hydrochloric acid, acetic acid or citric acid in an amount sufficient to adjust the pH of the overall composition to about 6.0, or below.

The composition of the present invention exhibits sustained periods of antimicrobial activity, particularly in the control of body odor.

As is known, an outstanding method for the control of body odor is to thoroughly wash the body with soap, but so prolific are the microbial flora of the skin that distinctive malodors tend to return within several hours after washing. To provide long periods of protection, there have been developed in the past compositions containing (a) astringents, such as aluminum chlorohydrate, which inhibit apocrine and eccrine gland secretions or (b) antimicrobial agents, such as hexachlorophene and trichlorocarbanilamide. Unfortunately, the former astringent compositions have limited value, since they have little or no control of microbial decomposition of debris and uncontrolled secretions and where there is control of secretions, such use suffers from severe short time limitations to obtain effective control. Nonetheless, the latter antimicrobial compositions have enjoyed widespread use. However, there have been recent investigations into topical and systemic toxicity of the named germicides used to control body odor. These investigations have led to severe restrictions, for instance, on the utilization of hexachlorophene and the recognition of the dangers of other germicides. Further, the use of astringents have only limited utility usually due to its harsh action on skin, particularly, on those who have sensitive skin. If a safe antimicrobial composition of low toxicity could be provided which would inhibit the development of body odor for relatively long periods of time, eg., at least twenty-four (24) hours, or longer, such a composition would satisfy a real need in the art.

It is a principal object of the invention to provide an antimicrobial composition of enhanced efficacy and safety which possesses broad spectrum activity in combating body odor and topical infections. It is a further object of the invention to provide an antimicrobial composition comprising at least an alkylsubstituted alanine surfactant and an alkyl-N,N-dimethylamine oxide or an acylamido t-amine oxide adjusted to a pH of 6.0, or below, so as to control gram positive bacteria, gram negative bacteria, fungi, and yeast, when topically applied. Other objects and advantages will become apparent from a consideration of the ensuing description.

According to the invention, there are provided antimicrobial compositions consisting essentially of a mixture of (a) an alkylsubstituted alanine, and (b) an alkyl-N,N-dimethylamine oxide, or an alkyl-N,N-dihydroxyethylamine oxide, or an acylamido t-amine oxide. The components are admixed at a temperature ranging from about 25° C to 80° C in a substantially aqueous or non-aqueous environment and adjusted to a pH of 6.0, or below, to provide a substantially uniform homogeneous composition having both enhanced broad spectrum activity and low toxicity.

In general, the alkylsubstituted alanine surfactant component of the composition can be written as:

1. RNHCH2 CH2 COOH, or

2. RN(CH2 CH2 COOH)2

where R is a higher alkyl having from 10 to 18 carbon atoms. Illustrative of such substitute alanine derivatives are N-cocoalanine, N-cetylalanine, N-stearylalanine, N-isostearylalanine, N-oleylalanine, N-stearyl-bis (2-aminopropionic acid), N-oleyl-bis (2-aminopropionic acid), N-coco-bis (2-aminopropionic acid), N-cetyl-bis (2-aminopropionic acid), N-lauryl-bis (2-aminopropionic acid), or mixtures of the same.

The alkyl-N,N-dimethylamine oxide, or alkyl-N,N-dihydroxyethylamine oxide, or acylamido t-amine oxide component of the aforementioned mixture, respectively has the respective structure: ##STR1## where R1 is a higher alkyl from 10 to 18 carbon atoms, as for instance, radicals such as decyl, undecyl, lauryl, tridecyl, myristyl, cetyl, stearyl, isostearyl, oleyl or mixtures of the same. Exemplary of the latter amine oxides are decyl-N,N-dimethylamine oxide, lauryl-N,N-dimethylamine oxide, stearyl-N,N-dimethylamine oxide, oleyl-N,N-dimethylamine oxide, cocoamidotrimethylene-N,N-dimethylamine oxide, stearylamidotrimethylene-N,N-dimethylamine oxide, decyl-N,N-dihydroxyethylamine oxide, lauryl-N,N-dihydroxyethylamine oxide, coco-N,N-dihydroxyethylamine oxide, stearyl-N,N-dihydroxyethylamine oxide, oleyl-N,N-dihydroxyethylamine oxide, and mixtures of the same.

In general, the protonating agent necessary to supply the required pH to the overall composition is, for instance, any inert organic or inorganic acid, such as hydrochloric acid, phosphoric acid, sulfuric acid, citric acid, acetic acid, nicotinic acid, and the like. A good operating pH range for the overall composition is 4.0 to 6.0 and, preferably, from about 4.7 to 5.2. The pH of an aqueous solution comprising the above enumerated components of the invention is determined by employing 0.5%, by weight, of active components at a glass electrode to precisely define the acidity of the composition.

In practice, each of the components of the overall composition ranges widely from 0.1 part to 40.0 parts and the balance an inert solvent, such as water or a lower monohydric aliphatic alcohol for a total of at least 100 parts. Where water is employed, small amounts of lower alkyl alcohols may also be added thereto to provide ease in formulation. The pH of the total composition is then adjusted to the requisite pH by adding a suitable inorganic or organic acid thereto. The composition can be employed as a solution or as a spray, such an aerosol spray, utilizing commercially available "Freon" fluorocarbon or equivalent propellant.

Advantageously, the compositions of the present invention possess an extremely low toxicity exhibiting as an LD50 in Swiss-Webster mice greater than four (4) grams per kilogram by intraperitoneal or oral administration. Further, there are observed a lack of primary irritation to the skin and less eye irritation as compared with ordinary soap.

It has been found that the aforementioned compositions can be used in a plurality of ways. For instance, when applied to pyogenic wound infections, rapid healing is promoted. When used as an ear douche, the compositions can relieve ear infections and eliminate those mild microbial infections known as dandruff, crotch itch, athletes foot and the like. As stated above and as shown in the examples hereinbelow set forth, when the compositions of the invention are employed as a general personal body wash, body odor in the axillary and anal/genital areas in particular will be inhibited for periods in excess of twenty-four (24) hours and usually, will exhibit inhibition from seventy-two (72) to ninety-six (96) hours.

In order to facilitate a further understanding of the invention, the following examples are presented primarily for purposes of illustrating certain more specific details thereof. The invention is not to be deemed as limited thereby except as defined in the claims. Unless otherwise noted, all parts and percentages are by weight.

EXAMPLE 1

In this example, several compositions are prepared and used as a body wash. Twelve panels each consisting of five men and five women as subjects are selected and supplied with samples of the compositions herein defined in Table I below. After twenty-four (24) hours have elapsed since the panel members' last washing, each is instructed to wash, noting particularly the axillary odor before and after washing. The panel members are then examined during the next twenty-four (24) hours and longer for the time span when typical body odors develop. These times are then noted and recorded in Table I below.

                                  TABLE I__________________________________________________________________________                            Average ElapsedPanel                            Time Body Odor isNo.           Composition        Detected (hours)__________________________________________________________________________1.  Cocoamido-N,N-dimethylamine oxide-12%    actives in distilled water (pH=7)                              82.  Cocoamido-N,N-dimethylamine oxide-12%    actives in distilled water - pH adjusted    to 5.4 with citric acid        103.  N-oleylalanine-12% actives in distilled    water - pH measured at 6.2     124.  N-cocoalanine-12% actives in distilled    water - pH adjusted to 5.4 with citric acid                              125.  N-cetylalanine-6% in distlled water, plus    coco-N,N-dimethylamine oxide-6% in distilled    water at pH=6.4                126.  N-cocoalanine-6% in distilled water, plus    cocoamido-N,N-dimethylamine oxide-6% in    distilled water citric acid-0.55% in dis-    tilled water at a pH=5. with citric acid                              48-967.  N-cetylalanine-4% in distilled water, plus    myristyl/palmitic-N,N-dimethylamine oxide-    6% in distilled water, adjusted to pH=5 with acetic    acid                           48-728.  N-isostearylalanine-6% in distilled water, plus    Oleyl-N,N-dimethylamine oxide-6% in dis-    tilled water, adjusted to pH=5.5 with    citric acid                    48-609.  70/30 Myristyl/palmitic-N,N-dimethylamine    oxide-12% in distilled water-pH adjusted    to 5.5 with citric acid        1210. Decyl-N,N-dimethylamine oxide-12% actives    in distilled water-pH adjusted to 5.2    with acetic acid               811. 70/30 Myristyl/palmitic-N,N-dimethylamine    oxide-6% + lauryl-N,N-dimethylamine oxide-    6% in distilled water, adjusted to a pH=    5.2 with citric acid           1012. 70/30 Myristyl/palmitic-N,N-dihydroxyethylamine oxide-    12% actives in distilled water - pH adjusted to 5.1    with citric acid               12__________________________________________________________________________

From the above table, it can be clearly seen that the compositions of the present invention at the adjusted pH range cause a marked improvement in body odor inhibition.

EXAMPLE 2

The relation between antimicrobial activity and control of body odor is determined by subjecting each of the panel members of Example 1 to additional washing tests employing the compositions of Example 1. There are obtained the density of microbes in the axillary area of each panelist by using a Rodac plate comprising Tryptose soy agar with TweenŽ 80 and lecithin to neutralize residual germicide. The panelist presses the plate for 30 seconds to the axillary area of the armpit. The plates are then incubated at 37° C for 24 hours and the number of colonies are counted. The density in the colonies per square inch is next calculated. The data obtained are noted in the table below and are the average values of the subjects treated.

              TABLE II______________________________________    0         12        24      48Composition of    Hours after              Hours after                        Hours after                                Hours afterExample 1    washing   washing   washing washing______________________________________1        1000      2400      TNC*    TNC2        1200      2500      TNC     TNC3        2800      TNC       TNC     TNC4        1200      2500      TNC     TNC5        1300      2000      TNC     TNC6         450       900      1200    17507         200       450      850     1000______________________________________ *TNC means too numerous to count - the density is greater than 3000 colonies per square inch.
EXAMPLE 3

There are admixed at 40° C N-stearylalanine (6.25 gm.), coco-N,N-dimethylamine oxide (13 gm.) citric acid (4.5 gm.) and 125 gm. of distilled water. The pH of the mixture when diluted to 0.5% actives is equal to 5.0.

The mixture is tested as a body shampoo and after 60 hours subsequent to washing, the panel reported no evidence of body odor in the axillary areas.

EXAMPLE 4

A mixture of N-stearylalanine (6.5 gms.), coco-N,N-dimethylamine oxide (13 gms.), acetic acid (4.5 gms.), and 66 gms. of water, formed at 50° C and having a pH on dilution is equal to 5.1, is employed as a body wash as in Example 3 above. Body odor is absent after seventy-two (72) hours.

Substituting hydrochloric acid for acetic acid in the above mixture, a similar result is noted.

EXAMPLE 5

There are admixed N-cetylalanine (2.5 gms.), myristyl-N,N-dimethylamine oxide (5.5 gms.), citric acid (2.0 gms.) and 87 gms. of water. The mixture is heated to 60° C and the pH determined on dilution is 5.5.

As in Example 4 above, the mixture is used as a body wash to determine axillary and pubic body odors. After 72 hours subsequent to washing, no body odor is detected. Moreover, panel members with dandruff report complete control of dandruff after two days' use when washing once each day with the above composition.

EXAMPLE 6

A mixture of N-laurylalanine (5.2 gms.), 70/30 myristyl/palmitic-N,N-dimethylamine oxide mixture (5.5 gms.) citric acid (0.7 gms.) and water (108 gms.) is heated to 35° C. The pH of the diluted solution is 5.4 and is used as a body wash. No body odor is detected for seventy-two (72) hours after washing.

EXAMPLE 7

There are added at 30° C. 6.2 gms. of N-coco-bis (2-aminopropionic acid), 6.2 gms. of 70/30 myristyl/palmitic-N,N-dimethylamine oxide, 5. gms. of isopropanol, 0.7 gm. of citric acid, and 92 gms. of water. Upon dilution, the pH measured equals 5.5.

The mixture is used as a body shampoo and controls body odor for 48 hours after washing in all panel members.

EXAMPLE 8

There are admixed at 75° C. 10 gms. of N-cetyl-bis (2-aminopropionic acid), 10 gms. of coco-n-betaine, 42 gms. of 70/30 myristyl/palmitic-N,N-dimethylamine oxide, 15 gms. of isopropanol, 9 gms. of citric acid, and 550 gms. of water. There is obtained a solution having a pH=5.0 on dilution and the preparation when used as a body wash controls odor for more than 72 hours after washing.

EXAMPLE 9

This example illustrates the formulation of a solid composition comprising of 32 gms. of N-stearyl-bis (2-aminopropionic acid), 32 gms. of myristyl/palmitic-N,N-dimethylamine oxide, 20 gms. of isopropanol, 40 gms. of water and 6.3 gms. of citric acid. The mixture is vigorously stirred and heated to a temperature of 80° C. Resultant composition is then dried by evaporation and cooled. There is recovered 110 gms. of a waxy solid product having a pH equal to 5.0 at a 0.5% aqueous concentration.

The solid composition is employed as solid detergent for washing and controls body odor for 48 hours after washing.

EXAMPLE 10

In this example there is prepared a spray composition. There are admixed 0.1 gm. N-cetyl-bis (2-aminopropionic acid), 0.1 gm. coco-N,N-dihydroxyethylamine oxide, 10 gms. isopropanol, and 0.02 gm. of citric acid. The mixture is heated to 40° C, cooled, and admixed with 100 gms. of liquified butane in a suitable container.

Resultant composition is sprayed under the armpits of several panelists. Each reports underarm odor control for at least 48 hours after use.

EXAMPLE 11

There are added to a suitable mixing vessel with stirring 8 gms. of N-cocoalanine, 8 gms. of N-isostearyl- bis (2-aminopropionic acid), 16 gms. of 70/30 myristyl/palmitic-N,N-dimethylamine oxide, 3.3 gms. of citric acid and q.s. to 250 gms. of water. Resultant mixture is stirred vigorously and heated to 60° C for 15 minutes.

Upon cooling, the pH of the mixture is found to possess a pH equal to 4.7 on dilution.

Resultant composition is employed as a body wash following the procedure of Example 2 above. After 12 hours, it is found by each of five panelists that after 12 hours, no body odor is detected and bacterial count of 190 colonies per square inch is obtained. After 36 hours, no body odor is reported and the bacterial count rose to 600 colonies per square inch. The controls, however, in 36 hours all reported detectable body odor and bacteria colonies too numerous to count, when each of the controls constituting five panelists employs a modified composition of this example in which citric acid is omitted. The pH of the latter composition, on dilution, is 7.4.

Advantageously, the compositions of the present invention, and particularly, as exemplified in each of the above examples, are employed in successfully treating pyogenic infections. The treatment consists of cleaning the wound by washing the same with the composition of the invention and then covering the wound for about 4 to 5 hours. In all cases, irritation and inflammation cease within the four to five hour period, and most wounds exhibit satisfactory healing within two to three days thereafter.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3484523 *Dec 27, 1966Dec 16, 1969Millmaster Onyx CorpQuaternary ammonium-tertiary amine oxide compositions
US3697655 *Oct 28, 1969Oct 10, 1972American Cyanamid CoGermicidal detergent compositions in controlling dandruff
Non-Patent Citations
Reference
1Kirk-Othmer Encyc. of Chem. Tech., 2nd Ed., 09231977 19 (1969), pp. 555-566, 575-577.
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4258063 *Jun 23, 1978Mar 24, 1981Henkel CorporationSelf-emulsifying cosmetic base
US4839158 *Jul 31, 1987Jun 13, 1989E. B. Michaels Research Associates Inc.Process and composition for oral hygiene
US5059625 *Oct 1, 1990Oct 22, 1991Olin CorporationPolyglycidol amine oxide surfactants having antimicrobial activity
US5266598 *Aug 11, 1992Nov 30, 1993Maruishi Pharmaceutical Co., Ltd.Skin disinfectant compositions
US5275804 *Sep 25, 1992Jan 4, 1994E. B. Michaels Research Associates, Inc.Process and composition for oral hygiene
US5314917 *Mar 22, 1991May 24, 1994E. B. Michaels Research Associates, Inc.Method for inactivating enveloped viruses and sperm
US5389676 *Sep 13, 1993Feb 14, 1995E. B. Michaels Research Associates, Inc.Viscous surfactant emulsion compositions
US5658749 *Feb 23, 1995Aug 19, 1997Corning Clinical Laboratories, Inc.Method for processing mycobacteria
US5968539 *Jun 4, 1997Oct 19, 1999Procter & Gamble CompanyMild, rinse-off antimicrobial liquid cleansing compositions which provide residual benefit versus gram negative bacteria
US6004771 *Aug 11, 1997Dec 21, 1999Integrated Research Technology, LlcMethod for processing mycrobacteria
US6183757Jun 4, 1997Feb 6, 2001Procter & Gamble CompanyMild, rinse-off antimicrobial cleansing compositions which provide improved immediate germ reduction during washing
US6183763Jun 4, 1997Feb 6, 2001Procter & Gamble CompanyAntimicrobial wipes which provide improved immediate germ reduction
US6190674Jun 4, 1997Feb 20, 2001Procter & Gamble CompanyLiquid antimicrobial cleansing compositions
US6190675Nov 12, 1997Feb 20, 2001Procter & Gamble CompanyMild, rinse-off antimicrobial liquid cleansing compositions which provide improved residual benefit versus gram positive bacteria
US6197315Jun 4, 1997Mar 6, 2001Procter & Gamble CompanyAntimicrobial wipes which provide improved residual benefit versus gram negative bacteria
US6210695Jun 4, 1997Apr 3, 2001The Procter & Gamble CompanyLeave-on antimicrobial compositions
US6214363Nov 12, 1997Apr 10, 2001The Procter & Gamble CompanyLiquid antimicrobial cleansing compositions which provide residual benefit versus gram negative bacteria
US6242486Oct 10, 1997Jun 5, 2001Integrated Research Technology, LlcLong chain carboxybetaines in antimicrobial formulations
US6284259Nov 12, 1997Sep 4, 2001The Procter & Gamble CompanyAntimicrobial wipes which provide improved residual benefit versus Gram positive bacteria
US6287577Nov 12, 1997Sep 11, 2001The Procter & Gamble CompanyLeave-on antimicrobial compositions which provide improved residual benefit versus gram positive bacteria
US6287583Nov 12, 1997Sep 11, 2001The Procter & Gamble CompanyLow-pH, acid-containing personal care compositions which exhibit reduced sting
US6297278Apr 4, 1994Oct 2, 2001Biosyn Inc. (A Pennsylvania Corporation)Method for inactivating sexually transmitted enveloped viruses
US6616922Mar 27, 2001Sep 9, 2003The Dial CorporationAntibacterial compositions
US6770268 *May 21, 2003Aug 3, 2004Oratec Corp.Non-foaming anti-infective periodontic compositions
US7091166 *Mar 20, 2002Aug 15, 2006Henkel Kommanditgesellschaft Auf AktienAcidic, phosphate-free plastic cleaner composition with reduced mild steel equipment etch for cleaning plastic parts
EP0733361A2 *Jul 17, 1991Sep 25, 1996E.B. Michaels Research Associates, Inc.Method for inactivating enveloped viruses and sperm
WO1987004922A1 *Feb 17, 1987Aug 27, 1987Michaels E B Res Ass IncProcess and composition for oral hygiene
WO1988004315A1 *Dec 11, 1987Jun 16, 1988Wickford Corp New JerseyComposition for the removal of indelible stains from the human epidermis and the reconditioning and cleaning of processed animal skins
WO1992016201A1 *Jul 17, 1991Oct 1, 1992Michaels E B Res AssMethod for inactivating enveloped viruses and sperm
Classifications
U.S. Classification514/561, 510/133, 510/384, 510/503, 510/477, 510/488, 510/433, 510/131, 510/382, 510/480, 514/625, 514/644
International ClassificationC11D3/00, A01N37/20, A61K31/195, A61Q19/10, A61Q5/02, C11D1/94, A61K31/205, A61Q15/00, A01N37/46, A01N41/04, A01N33/24, C11D3/48, C11D1/75, A01N37/44, A61K8/44, A61K8/40
Cooperative ClassificationA61K8/40, C11D3/0068, A61Q17/005, A61Q5/02, A61K31/205, A61Q15/00, C11D3/48, A01N33/24, C11D1/75, A01N41/04, A01N37/44, A01N37/20, A61K8/44, C11D1/94, A01N37/46, A61Q19/10
European ClassificationC11D3/48, A01N41/04, A01N37/46, A01N37/20, A01N37/44, A61K31/205, A61Q15/00, A61K8/40, C11D1/75, A61Q5/02, A61K8/44, C11D1/94, C11D3/00B14, A61Q19/10, A01N33/24, A61Q17/00F
Legal Events
DateCodeEventDescription
Mar 12, 1993ASAssignment
Owner name: E.B. MICHAELS RESEARCH ASSOCIATES, INC., CONNECTIC
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:MICHAELS, EDWIN B.;REEL/FRAME:006457/0695
Effective date: 19930309
Oct 15, 1996ASAssignment
Owner name: BIOSYN, INC. (A PENNSYLVANIA CORPORATION), PENNSYL
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:E.B. MICHAELS RESEARCH ASSOCIATES, INC. (A CONNECTICUT CORPORATION);REEL/FRAME:008178/0368
Effective date: 19961008